The main purpose of this project is to study pancreatic glucagon secretion under physiological and pathological conditions including experimentally induced diabetes mellitus. Islets of Langerhans will be isolated by a standard method from normal rats which have been variously treated in vivo. Glucagon and insulin secretions will be measured during perifusion of such islets with media containing known or potential secretagogues and inhibitors. In the first instance it is hoped to confirm increased glucagon secretion by the islets of fasting, hypoglycemic and diabetic rats in response to stimuli such as arginine. using metabolites, hormones and other humoral agents added to such media in vitro, it is hoped to obtain effects which will explain metabolic derangements associated with abnormal glucagon secretion in vivo. Attempts will also be made to produce antiglucagon sera sufficiently specific and active for use in sensitive immunoassays of glucagon.